Abstract
Introduction:
Despite improvements in device technology, only one-third of stroke patients undergoing endovascular thrombectomy (EVT) achieve first-pass effect (FPE). We investigated the effect of arterial tortuosity and thrombus characteristics on the relationship between first-line EVT strategy and angiographic outcomes.
Patients and methods:
Patients with thin-slice baseline CT-angiography from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of acute ischemic stroke) were included. Tortuosity was estimated using the tortuosity index extracted from catheter pathway, and radiological thrombus characteristics were length, non-contrast density, perviousness and hyperdense artery sign. We assessed the association of first-line EVT strategy (stent-retriever [SR] versus contact aspiration [CA] versus combined SR+CA) with FPE (eTICI score 2c/3 after one pass), final eTICI 2b/3, number of passes and procedure duration using multivariable regression. Interaction of tortuosity and thrombus characteristics with first-line technique were assessed using interaction terms.
Results:
Among 520 included patients, SR as a first-line modality was used in 165 (31.7%) patients, CA in 132 (25.4%), and combined SR+CA in 223 (42.9%). FPE was observed in 166 patients (31.9%). First-line strategy was not associated with FPE. Tortuosity had a significant effect on FPE only in the CA group (aOR = 0.90 [95% CI 0.83–0.98]) compared with stent-retrievers and combined first-line approach (p interaction = 0.03). There was an interaction between thrombus length and first-line strategy for number of passes (p interaction = 0.04). Longer thrombi were associated with higher number of passes only in the CA group (acOR 1.03 [95% CI 1.00–1.06]).
Conclusion:
Our study suggests that vessel tortuosity and longer thrombi may negatively affect the performance of first-line contact aspiration catheters in acute stroke patients undergoing EVT.
Keywords: Stroke, endovascular thrombectomy, ischemic, thrombus, reperfusion
Introduction
Endovascular thrombectomy (EVT) is the current standard of care for treatment of anterior circulation stroke with large vessel occlusion (LVO). 1 Fast and effective recanalization of the occluded artery during EVT directly impacts clinical outcomes. Excellent reperfusion after one pass – that is, first pass effect (FPE) - should be the aim of every EVT procedure. 2
Although prior randomized trials showed similar angiographic and clinical outcomes between different first-line EVT strategies (stent retriever alone (SR) versus contact aspiration alone (CA) versus combined strategy (SR and CA)),3–5 it is unclear whether the effect of first-line strategy on angiographic outcomes is modified by vessel anatomy and radiological thrombus characteristics. Prior studies have shown higher efficacy of SR in red blood cell-rich thrombi, whereas CA were more efficient in fibrin-rich thrombi. The presence of hyperdense artery sign or susceptibility vessel sign was used as a marker of red blood cell content.6,7
Vessel tortuosity and thrombus characteristics can be estimated visually, quantitatively, or both.8–12 Although visual assessments are faster and might be useful for outcome prediction in the acute setting, it has a lower accuracy which could lead to poor estimation of procedural outcomes compared to quantitative assessments. Identification of factors on baseline imaging that could be associated with a better performance of an EVT device rather than another can help neurointerventionists plan the procedure and avoid delays in restoration of cerebral blood flow. Here, we present data from a large multicenter randomized controlled trial using quantitative estimates. Our aim is to investigate the effect of arterial tortuosity and radiological thrombus characteristics on the relationship between first-line strategy and procedural outcomes in acute stroke patients who underwent EVT.
Methods
Patient population
Data are from the randomized controlled ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of acute ischemic stroke), a multicenter trial evaluating the safety and efficacy of nerinetide in acute ischemic stroke patients with large vessel occlusion undergoing EVT. 13 Study approval was obtained from the ethics board at each site and the responsible regulatory authorities. Signed informed consent was obtained from the patients or their legally authorized representatives. Study data are available from the corresponding author upon reasonable request.
Methods and inclusion criteria of the ESCAPE-NA1 trial have been previously reported. 13 Briefly, patients were eligible if: age ⩾18 years with large vessel occlusion in the anterior circulation (intracranial internal carotid artery [ICA], middle cerebral artery (MCA) M1 or all M2 branches), baseline National Institutes of Health Stroke Scale (NIHSS) >5, time from last seen well to randomization ⩽12 h, pial collateral filling ⩾50% of the ischemic MCA territory, and Alberta Stroke Program Early CT Score >5. All patients underwent non-contrast CT (NCCT) and single-phase or multiphase CT angiography (CTA) at baseline. All patients received EVT with or without intravenous thrombolysis according to clinical routine eligibility.
For this study, we included ESCAPE-NA1 patients with baseline thin-slice NCCT and head and neck CTA in whom EVT was attempted through groin puncture. We excluded cases with (a) motion or beam hardening artifacts (n = 14), (b) irremediable co-registration errors of head NCCT and CTA (n = 12), (c) poor arterial opacification on baseline CTA (n = 4), (d) incomplete CTA coverage of the neck (n = 10), (e) failure of centerlines extraction and processing (n = 30), and (f) missing first-line technique (n = 12) Figure 1). The choice of first-line thrombectomy strategy was left to the discretion of the operator. We defined three groups according to the strategy of first attempt: stent retriever, contact aspiration, and combined strategy (stent retriever plus contact aspiration).
Figure 1.
Study flow chart. CTA: computed tomography angiography; ESCAPE-NA1: efficacy and safety of nerinetide for the treatment of acute ischemic stroke; EVT: endovascular therapy; NCCT: non-contract computed tomography; FPE: first-pass effect.
Image processing analysis
An independent imaging core lab blinded to all clinical data assessed the following characteristics: Alberta Stroke Program Early CT score on baseline noncontrast CT, collateral grade, occlusion location on baseline NCCT and CTA. Reperfusion grade was scored by the same core lab on DSA images according to the expanded Thrombolysis in Cerebral Infarction (eTICI) score. 14
Thrombus characteristics extraction
Baseline NCCT images were automatically co-registered onto baseline CTA images using rigid registration with the SimpleITK toolbox in Python. 15 Manual annotation of intracranial thrombi was performed by five trained readers (FB, MK, PC, BJK, and NS), who were blinded to all clinical data. Three regions of interest with a radius of 1 mm were placed in the proximal, middle and distal part of the thrombus as described previously.11,16 In addition, one marker was placed on the proximal thrombus border, and one marker on the distal thrombus border. We analyzed four thrombus characteristics: (1) thrombus length (in mm, from proximal border to distal border marker through proximal, middle and distal intra-thrombus markers), (2) absolute density (in Hounsfield Units [HU], mean density of three intra-thrombus markers on NCCT), (3) thrombus perviousness (in HU, difference in mean density of intrathrombus marker regions between NCCT and CTA, caused by CTA contrast inflow), and (4) hyperdense artery sign (HAS, assessed visually by the readers on thin-slice NCCT and considered present if the occluded artery was visually denser than the contralateral vessel).
Processing pipeline of tortuosity measurement
(1) Centerline annotation and extraction: Neck CTA Digital Imaging and Communications in Medicine (DICOM) images were loaded onto the CVI42 software (Circle Cardiovascular Imaging, Calgary, Canada). Four trained readers (FB, PC, NS and BJK) used available tools in CVI42 software (3D region growing and seed points) to trace arterial centerlines from the aortic arch (proximal to the left subclavian artery origin) to the intracranial occlusion site (Figure 2). The centerline points were then exported from CVI42 to an xml workspace file which was then used to generate the corresponding Neuroimaging Informatics Technology Initiative (NIfTI) files for additional processing.
(2) Annotation of arterial segments: The centerline NIfTI file was imported in ITK-SNAP and loaded over the CTA volume. Using manual markers at five points (aortic origin of carotid artery (brachiocephalic trunk or left common carotid artery), origin of cervical ICA, carotid canal within temporal bone where the carotid artery enters the middle cranial fossa, ICA terminus, and proximal border of intracranial thrombus), the centerlines were divided into five arterial segments to assess segmental tortuosity. These segments were: aortic arch, common carotid artery (including brachiocephalic trunk if right side pathway), cervical ICA, intracranial ICA, and middle cerebral artery until the proximal thrombus border (Supplemental Figure 1). In case of intracranial ICA occlusion, the marker at the ICA terminus was not placed.
(3) Tortuosity measurement: Since there is no standardized method of assessing tortuosity, we used a common measure of vascular tortuosity, that is tortuosity index (TI).10,17,18 Using a MATLAB algorithm, the TI was computed for each individual segment using the formula: Tortuosity index = 1 − (Euclidean distance between two endpoints/actual length along the vessel’s centerline) (Supplemental Figure 2). The index ranges from 0 to 1 with higher values indicating a more tortuous vessel. TI was used in previous studies to assess arterial tortuosity.9,19 TI was calculated for the entire vessel path and for two additional compound segments using the same formula. These were: (1) extracranial TI which included aortic arch, common carotid artery (with brachiocephalic artery if right side centerline), and cervical ICA; (2) intracranial TI comprised of ICA from the carotid canal to its terminus and M1-MCA segment until the proximal end of the thrombus.
Figure 2.
Processing pipeline of tortuosity measurement. (a–c) Centerline annotation in patient with left distal M1-middle cerebral artery (MCA) occlusion using region growing and seed points was carried out in CVI42 software (Circle Cardiovascular Imaging, Calgary, Canada). The centerline was then divided into five arterial segments by adding five markers on ITK-SNAP software. Locations of the markers were: origin of brachiocephalic trunk or left common carotid artery (CCA), origin of cervical internal carotid artery (ICA), carotid canal within petrous bone, ICA terminus, and proximal end of thrombus. (d) The extracted centerline was then imported in MATLAB and tortuosity indexes were calculated for each segment and for multiple segments together (aortic arch + CCA + cervical ICA, and intracranial ICA+ MCA).
Outcomes
The primary outcome was FPE, defined as eTICI 2c-3 after one EVT pass. Secondary outcomes were successful reperfusion (final eTICI 2b-3), total number of passes, total procedure duration (arterial access to last intracranial angiography run), and procedural complications (arterial perforation, dissection, and emboli in a new territory).
Statistical analyses
Patient characteristics, imaging variables, and treatment details were compared between patients with first-line SR versus CA versus combined strategy using Chi square test and Kruskal-Wallis test as appropriate.
We assessed the association of first-line EVT strategy, thrombus characteristics and tortuosity index with procedural outcomes using univariable and multivariable regression models. Adjustments were made for age, sex, baseline NIHSS, occlusion site (MCA vs ICA), history of atrial fibrillation, stroke onset to arterial puncture time, and use of balloon guide catheter (BGC). Because procedural complications were rare, we only adjusted for age to avoid overfitting.
Logistic regression was used for binary outcomes and linear regression for the continuous outcome (procedure duration) which were log10 transformed, to better meet the assumption of normally distributed residuals in linear regression. For the number of passes model, ordinal logistic regression was used. Model’s assumption was tested using Brant’s (proportional odds) test and was met. Moreover, multicollinearity was assessed using variation inflation factor and pairwise correlation and no significant collinearity was found.
The influence of tortuosity and radiological thrombus characteristics on the association between first-line EVT strategy and outcomes was assessed using multiplicative interaction terms (first-line strategy × tortuosity or first-line strategy × thrombus characteristics) in the multivariable regression models.
Statistical significance was defined as two-tailed p < 0.05. No imputation was performed as missing data were minimal. All analyses were performed using Stata/MP 17.0 (STATA LLC, Corp).
Results
Patient characteristics
A total of 520 patients with available thrombus annotations and tortuosity measurements in whom EVT was attempted were included in this study (Figure 1). Baseline characteristics were similar between included and excluded patients (Supplemental Table 1).
Median age was 70 years (interquartile range [IQR 60–79], and 2275 (48.8%) were females. Median baseline NIHSS score was 17 (IQR 13–21), and median time from stroke onset to puncture was 204 min (IQR 135–338). SR as a first-line modality was used in 165 (31.7%) patients, CA in 132 (25.4%), and combined SR and CA in 223 (42.9%). Median thrombus length, density and perviousness were 25.8 (IQR 18–37) mm, 50 (IQR 43–54) HU, and 11 (IQR 5–20) HU, respectively. HAS was seen in 336 (64.9%) patients, and median tortuosity index was 0.29 (IQR 0.25–0.34). Patients with first-line combined strategy had higher proportions of diabetes and hyperlipidemia, and first-line SR strategy was more commonly used with BGC (Table 1).
Table 1.
Baseline characteristics stratified by first-line thrombectomy strategy.
| Stent retriever (n = 165) | Aspiration only (n = 132) | Combined SR and CA (n = 223) | p Value | |
|---|---|---|---|---|
| Age | 68 (58-78) | 69 (60-80) | 71 (60-80) | 0.21 |
| Sex, women | 84 (49.1) | 67 (50.8) | 118 (52.9) | 0.75 |
| Medical factors | ||||
| Diabetes mellitus | 19 (11.5) | 23 (17.4) | 57 (25.6) | 0.01 |
| Hypertension | 105 (63.6) | 95 (72.0) | 162 (72.6) | 0.13 |
| Hyperlipidemia | 58 (35.1) | 60 (45.4) | 111 (49.8) | 0.02 |
| Atrial fibrillation | 52 (31.5) | 43 (32.6) | 82 (36.8) | 0.51 |
| History of stroke or TIA | 15 (9.1) | 16 (12.2) | 35 (15.7) | 0.16 |
| Stroke presentation | ||||
| Baseline NIHSS | 16 (12-21) | 18 (13-21) | 17 (13-20) | 0.81 |
| Wakeup stroke | 26 (15.7) | 16 (12.1) | 35 (15.7) | 0.60 |
| Onset to puncture time (min) | 205 (126–338) | 212 (146–326) | 188 (136–385) | 0.58 |
| IV alteplase | 97 (58.8) | 82 (62.1) | 120 (53.8) | 0.29 |
| Stroke etiology | 0.69 | |||
| Cardioembolic | 94 (56.9) | 79 (69.8) | 125 (56.0) | |
| LAA | 37 (22.4) | 32 (24.2) | 48 (21.5) | |
| Other (ESUS, undetermined) | 34 (20.6) | 21 (15.9) | 50 (22.4) | |
| Imaging factors | ||||
| ASPECTS | 8 (7-8) | 8 (7-9) | 8 (7-9) | 0.34 |
| Collaterals | 0.77 | |||
| Poor | 6 (3.7) | 7 (5.3) | 7 (3.1) | |
| Moderate | 133 (81.6) | 107 (81.1) | 177 (79.7) | |
| Good | 24 (14.7) | 18 (13.6) | 38 (17.1) | |
| Carotid tandem lesion | 17 (10.3) | 12 (9.1) | 22 (9.9) | 0.94 |
| Occlusion site | 0.17 | |||
| ICA | 45 (27.3) | 26 (19.7) | 42 (18.8) | |
| M1-MCA | 114 (69.1) | 101 (76.5) | 177 (79.4) | |
| M2-MCA | 6 (3.6) | 5 (3.8) | 4 (1.8) | |
| Thrombus characteristics | ||||
| Thrombus length (mm) | 25 (17-36) | 26 (18-35) | 25 (18-38) | 0.72 |
| Thrombus density (HU) | 50 (44-54) | 50 (44-55) | 49 (42-55) | 0.43 |
| Perviousness (HU) | 14 (7-23) | 10 (4-16) | 10 (4-20) | 0.001 |
| HAS | 116 (60.1) | 107 (70.4) | 116 (64.4) | 0.14 |
| Tortuosity index | 0.29 (0.26–0.33) | 0.29 (0.25–0.34) | 0.30 (0.26–0.34) | 0.78 |
| Procedural characteristics | ||||
| Anesthesia | 0.06 | |||
| Local or conscious sedation | 121 (73.3) | 100 (75.7) | 185 (82.9) | |
| General anesthesia | 44 (26.7) | 32 (24.2) | 38 (17.0) | |
| Use of BGC | 138 (97.2) | 19 (17.9) | 147 (69.7) | <0.001 |
| Outcomes | ||||
| FPE | 63 (38.2) | 36 (27.3) | 67 (30.0) | 0.10 |
| Final TICI 2b/3 | 155 (93.9) | 122 (92.4) | 203 (91.0) | 0.57 |
| Procedure duration, min | 50 (34–77) | 38 (23–61) | 49 (27–68) | <0.001 |
| Number of EVT attempts | 1 (1-2) | 1 (1-3) | 1 (1-2) | 0.98 |
| Procedural complications | 10 (6.1) | 5 (3.8) | 13 (5.8) | 0.66 |
Data are median (interquartile range) or n (%). ASPECTS: Alberta Stroke Program Early CT Score; BGC: balloon guide catheter; CA: contact aspiration; ESUS: embolic stroke of undetermined origin; EVT: endovascular thrombectomy; FPE: first-pass effect; HAS: hyperdense artery sign; LAA: large artery atherosclerosis; NIHSS: National Institutes of Health Stroke Scale; IV: intravenous; SR: stent retriever; TIA: transient ischemic attack; TICI: Thrombolysis in Cerebral Infarction.
Values in bold indicate that p<0.05
Primary outcome
FPE was observed in 166/520 (31.9%) patients. First-line EVT strategy was not associated with FPE in the univariable and multivariable analysis. BGC use was more common in the FPE group, however this association was not significant in the adjusted analysis. Regarding thrombus characteristics and arterial tortuosity, patients with FPE had shorter thrombi (median 23 mm [IQR 16–32] vs 27 mm [IQR 19–39], p = 0.002), and smaller intracranial tortuosity indices (median 0.53 [0.49–0.57] vs 0.55 [IQR 0.51–0.58], p = 0.03) compared to patients without FPE. Thrombus density, perviousness and HAS were not different between FPE and no-FPE groups (Supplemental Table 2). In the multivariable analysis, older age (adjusted odds ratio [aOR] 1.02 [95% confidence intervals 1.01–1.04]), shorter thrombi (aOR 0.97 [95% CI 0.95–0.99]), and lower intracranial tortuosity were associated with FPE (aOR 0.95 [95% CI 0.91–0.99]).
We observed a significant interaction for the effect of tortuosity when comparing first-line stent retrievers with aspiration alone (p = 0.03) but not when comparing with combined strategy (p = 0.41). In the aspiration-only group, higher tortuosity was associated with lower likelihood of FPE (aOR 0.90 [95% CI 0.83–0.98]), however, in both combined approach group (aOR 0.96 [95% CI 0.90–1.02]) and stent retriever alone group (aOR 0.99 [95% CI 0.93–1.06]), tortuosity was not significantly associated with FPE (Supplemental Figure 3). There was no interaction between any thrombus characteristics (thrombus length, perviousness, density and HAS) and first-line device for FPE (all p > 0.05, Supplemental Table 3).
Secondary outcomes
Successful reperfusion
Successful reperfusion (final TICI 2b/3) was achieved in 480/520 (92.3%) patients. First-line EVT strategy, tortuosity index and thrombus features were not significantly associated with this outcome in the adjusted analysis. There was no significant interaction between thrombus characteristics, tortuosity and first-line strategy for successful reperfusion.
Number of passes
In the univariable analysis, thrombus length (unadjusted common OR [ucOR] 1.01 [95% CI 1.00–1.02]) and extracranial TI was associated with an increased number of passes (ucOR 1.04 [95% CI 1.01–1.06]), however, no factor was associated with number of passes in the multivariable analysis.
We observed a significant interaction for the effect of thrombus length when comparing stent retrievers with aspiration alone (p = 0.04) but not when comparing with combined approach (p = 0.37). In the aspiration-only group, longer thrombi were associated with higher number of passes (acOR 1.03 [95% CI 1.00–1.06]), however, in both combined approach group (acOR 1.01 [95% CI 0.99–1.04]) and stent retriever alone group (acOR 0.99 [95% CI 0.96–1.01]), thrombus length was not significantly associated with number of passes. There was no interaction between tortuosity, other thrombus characteristics and first-line device for number of passes.
Total procedure duration
In the multivariable analysis, thrombus length (adjusted ß = 0.01 [95% CI 0.002–0.02]), extracranial vessel tortuosity (adjusted ß = 0.01 [95% CI 0.004–0.02]), and CA (adjusted ß = −0.22 [95% CI −0.42, −0.01]) were associated with procedural time. We observed no statistically significant interaction between thrombus characteristics, tortuosity and first-line EVT technique for procedure duration.
Procedural complications
Complications during EVT occurred in 28/520 (5.4%) patients: emboli to new territory in 22/520 (4.2%), vessel perforation in 4/520 (0.8%), and ICA dissection in 2/520 (0.4%) patients. Higher thrombus absolute density was associated with procedural complications (aOR 1.06 [95% CI 1.01–1.11]). Tortuosity index and other thrombus features were not significantly associated with this outcome. We did not find any interaction between thrombus characteristics, tortuosity and first-line strategy for procedural complications (Supplemental Table 3).
Discussion
In this post-hoc analysis of the ESCAPE-NA1 trial, we found evidence of interaction between tortuosity, thrombus length and first-line EVT technique for FPE and number of passes. Among patients treated with contact aspiration alone as first-line EVT strategy, the likelihood of FPE decreased with higher tortuosity and the number of passes increased with longer thrombi. This finding was not observed among patients treated with SR alone or combined SR+CA as first-line EVT strategy.
Our findings suggest that vessel tortuosity and thrombus length may serve as guide for device choice in EVT. Vessel anatomy is an important parameter in predicting procedural outcomes. Challenging anatomy and tortuous vessels are associated with lower recanalization rates and a higher rate of EVT failure. A registry data analysis of 592 patients from Switzerland reported that third of reperfusion failures (final eTICI 0–1) were attributed to cervical vessel tortuosity. 20 Identification and stratification of patients with vessel tortuosity before EVT is important for interventionists to improve device/technique selection and hence guarantee best possible care for such technically challenging cases. The differential effect of tortuosity on FPE across thrombectomy first-line strategy is in line with the results of Koge et al. who reported lower rates of FPE in first-line CA thrombectomy in tortuous vessels (15%vs 22% and 23%), although not statistically significant. 8 This finding may reflect kinking of the aspiration catheter lumen in very tortuous and angulated arterial segments resulting in lumen collapse and major reduction in power of suction. Another explanation could be related to axis misalignment between aspiration catheter and thrombus resulting in poor catheter-thrombus interaction. 21 Further studies of the influence of tortuosity on the efficacy of CA versus SR or SR+CA are warranted.
Our findings are consistent with previous studies showing a significant association of arterial tortuosity with FPE and procedure times, although the assessment and definitions of tortuosity vary between studies.8,19,22A single center study from Japan included 370 patients and assessed the internal carotid artery tortuosity visually, mainly on DSA images, for the presence of coiling, kinking, and the deflection of anterior and posterior genu of the cavernous segment. The authors found a lower chance of FPE, longer puncture to reperfusion times in the tortuous group. 8 Calculation of TI and degree of angulation in each carotid segment using quantitative 3D segmentations of vessel pathway on CTA in a study of 100 patients reported a significant but weak correlation between TI and both puncture to cervical and fluoroscopy times. 19 However, reperfusion rates were not described. Our study expands on these results by including the entire arterial pathway from the aortic arch to the intracranial occlusion location and uses a more comprehensive list of procedural outcomes in a large sample of patients.
Our results are in line with a previous report that did not find an interaction between thrombus density, HAS and first-line EVT strategy, 23 however, in another study, the authors found a significant interaction between HAS and first-line EVT technique, that is, better response to SR than CA for FPE in patients with hyperdense thrombi. 7 The difference with our results may be explained by the lack of standardized definition of HAS making its determination subjective. Moreover, imaging reads were not centrally adjudicated, and inter-reader agreement statistic was not reported in their study. 7
The interaction between thrombus length and first-line EVT was not previously reported. In a post-hoc analysis of the MR-CLEAN registry, there was no interaction of thrombus length and first-line EVT technique on FPE, successful reperfusion and procedure duration, however, number of passes was not assessed in this study. 23 This finding is important as number of passes was shown to be associated with worse outcomes after EVT. 24 This effect modification may be explained by the difference in mechanisms of device-thrombus interaction between SR and CA. SR interacts with the thrombus in its entire length, however, CA only engages the proximal segment of the thrombus, leaving its distal segment uncontrolled, especially in longer thrombi. Indeed, this was observed in vitro, where CA was associated with an increased risk of distal embolization. 25 Moreover, this finding is corroborated with the results of studies showing higher reperfusion rates of longer versus shorter SR.26,27
We acknowledge several limitations. First, many patients were excluded because of the non-availability of thin-section scans, therefore introducing selection bias, which is weighed against the measurement error caused by volume averaging in thick-slice scans. However, baseline characteristics between excluded and included patients were similar. Second, we only included one type of tortuosity measurement. Other markers such as degree of angulation and take-off angles may have improved the performance of our models, however, inclusion of the arterial segments proximal and distal to the common carotid origin (or brachiocephalic artery on right side) in the calculation of the tortuosity index is a proxy of the degree of the take-off angle (Supplemental Figure 4). Third, visual assessment of tortuosity was not performed and thus we were unable to compare the performance of both methods. Fourth, our findings do not apply to radial access EVT procedures since they were excluded from this study. Finally, other factors such as device dimensions and type were not available and therefore were not included in the analyses.
Conclusion
In patients with anterior circulation large vessel occlusion treated with EVT from the ESCAPE-NA1 trial, vascular tortuosity and longer thrombi influenced the efficacy of first-line CA compared to SR and combined technique. These findings could guide neurointerventionists to choose the best thrombectomy strategy to achieve fast and effective reperfusion. Larger prospective studies are warranted to confirm these results.
Supplemental Material
Supplemental material, sj-docx-1-eso-10.1177_23969873231183766 for Impact of vessel tortuosity and radiological thrombus characteristics on the choice of first-line thrombectomy strategy: Results from the ESCAPE-NA1 trial by Fouzi Bala, Petra Cimflova, Nishita Singh, Jianhai Zhang, Manon Kappelhof, Beom Joon Kim, Mohamed Najm, Rotem Golan, Ibukun Elebute, Faysal Benali, Nerea Arrarte Terreros, Henk Marquering, Charles Majoie, Mohammed Almekhlafi, Mayank Goyal, Michael D Hill, Wu Qiu and Bijoy K Menon in European Stroke Journal
Acknowledgments
We would like to thank Amor Bala and Wahiba Bala for their assistance and guidance in this research.
Footnotes
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Mohammed Almekhlafi reports grants from CIHR outside the submitted work, and serving on the scientific advisory board of Palmera Medical, Inc. Michael D Hill reports grants from CIHR during the conduct of the study, grants from Medtronic, and grants from NoNO Inc. outside the submitted work. In addition, he has a patent to US Patent office Number: 62/086,077 issued and licensed, and Director, Board of Circle Neurovascular, Director, Board of the Canadian Neuroscience Federation, and Director, Board of the Canadian Stroke Consortium. Mayank Goyal reports receiving fees from Medtronic, Stryker, Microvention, GE Healthcare, and Mentice. Charles Majoie reports grants from CVON/Dutch Heart Foundation, TWIN Foundation, European Commission, Healthcare Evaluation Netherlands, and Stryker outside the submitted work (all paid to institution); and is (minority interest) shareholder of Nicolab. Bijoy K Menon reports shares in Circle NVI; patent for systems of triage in acute stroke. Other authors report no conflict of interest. Fouzi Bala, Petra Cimflova, Nishita Singh, Jianhai Zhang, Manon Kappelhof, Beom Joon Kim, Mohamed Najm, Rotem Golan, Ibukun Elebute, Faysal Benali, Nerea Arrarte Terreros, Henk Marquering, and Wu Qiu report no relevant disclosures.
Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The ESCAPE-NA1 trial was supported by a grant from the Canadian Institutes of Health Research, by Alberta Innovates and NoNo.
Informed consent: Signed informed consent was obtained from the patients or their legally authorized representatives.
Ethical approval: Study approval was obtained from the ethics board at each site and the responsible regulatory authorities
Guarantor: Dr. Fouzi BALA
Contributorship: FBa: conceived the study idea, assisted in the analysis and wrote the paper. PC, NS, JZ, MK, BJK, MN, RG, IE, FBe: collected the data. NAT, HM, CM, MA, MG, MDH and WQ: provided critical inputs to the manuscript. BKM: designed and overviewed the study, provided critical inputs to the Manuscript.
ORCID iDs: Fouzi Bala 
https://orcid.org/0000-0001-6748-2081
Beom Joon Kim
https://orcid.org/0000-0002-2719-3012
Faysal Benali
https://orcid.org/0000-0002-1043-1125
Michael D. Hill
https://orcid.org/0000-0002-6269-1543
Supplemental material: Supplemental material for this article is available online.
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Supplementary Materials
Supplemental material, sj-docx-1-eso-10.1177_23969873231183766 for Impact of vessel tortuosity and radiological thrombus characteristics on the choice of first-line thrombectomy strategy: Results from the ESCAPE-NA1 trial by Fouzi Bala, Petra Cimflova, Nishita Singh, Jianhai Zhang, Manon Kappelhof, Beom Joon Kim, Mohamed Najm, Rotem Golan, Ibukun Elebute, Faysal Benali, Nerea Arrarte Terreros, Henk Marquering, Charles Majoie, Mohammed Almekhlafi, Mayank Goyal, Michael D Hill, Wu Qiu and Bijoy K Menon in European Stroke Journal